02146nas a2200241 4500000000100000008004100001653003000042653002400072653001200096653000800108100001500116700001600131700001400147700001500161700001000176700001000186700000900196700001200205700001500217245010800232520155100340022001301891 2015 d10aMycobacteria tuberculosis10aMycobacteria leprae10aleprosy10aDNA1 aDonoghue H1 aSpigelman M1 aO'Grady J1 aSzikossy I1 aPap I1 aLee O1 aWu H1 aBesra G1 aMinnikin D00aAncient DNA analysis – An established technique in charting the evolution of tuberculosis and leprosy3 a

Many tuberculosis and leprosy infections are latent or paucibacillary, suggesting a long time-scale for host and pathogen co-existence. Palaeopathology enables recognition of archaeological cases and PCR detects pathogen ancient DNA (aDNA). Mycobacterium tuberculosis and Mycobacterium leprae cell wall lipids are more stable than aDNA and restrict permeability, thereby possibly aiding long-term persistence of pathogen aDNA. Amplification of aDNA, using specific PCR primers designed for short fragments and linked to fluorescent probes, gives good results, especially when designed to target multi-copy loci. Such studies have confirmed tuberculosis and leprosy, including co-infections. Many tuberculosis cases have non-specific or no visible skeletal pathology, consistent with the natural history of this disease. M. tuberculosis and M. leprae are obligate parasites, closely associated with their human host following recent clonal distribution. Therefore genotyping based on single nucleotide polymorphisms (SNPs) can indicate their origins, spread and phylogeny. Knowledge of extant genetic lineages at particular times in past human populations can be obtained from well-preserved specimens where molecular typing is possible, using deletion analysis, microsatellite analysis and whole genome sequencing. Such studies have identified non-bovine tuberculosis from a Pleistocene bison from 17,500 years BP, human tuberculosis from 9000 years ago and leprosy from over 2000 years ago.

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